Stanniocalcin-1 (STC1) is a calcium-regulating hcrmone in bony fish. It is produced and stored in the corpuscle of Stannius, an accessory organ to the kidney. Elevation of ionized calcium in the fish plasma induces synthesis and secretion of STC1 into the blood. Upon circulation in the gill, it inhibits calcium influx from the aquatic environment, while in the gut, it inhibits calcium uptake. T'he mammalian homologue of this hormone is produced in multiple organs and is thought to function in an autocrine and/or paracrine manner. The cumulative data suggest that it inhibits calcium flux in cardiomyocytes, glut epithelium and neuronal cells. In neuronal cells, it is upregulated following ischemic injury and appears to have a cytoprotective effect in a manner that requires inhibition of calcium flux into the cells. Recent findings from our laboratory revealed striking upregulation of STC1 in the proximal tubules following ischemic or obstructive renal injury in humans. In addition, STC1 protein decorated the plasma membrane of inflammatory cells in the injured tissue. These findings suggested the involvement of STC1 in tissue inflammation, indeed, STC1 attenuated MCP1-mediated intracellular calcium increas and chemotaxis (using a trans-filter assay) in the macrophage-like Raw264.7 cells. The following specific aims are intended to elucidate the molecular mechanisms that underlie this process. Specific Aim I: will test the hypothesis that STC1 inhibits chemotaxis in other mononuclear cells (lymphocytes) in a manner that involves alterations in intracellular calcium currents. Specific Aim II: will examine the hypothesis that STC1 is an anti-inflammatory molecule. This will be tested using STC1 in an in vivo model of rat (WKY) anti-GBM (glomerular basement membrane) glomerulonephritis.